One of the signature characteristics of drugs targeting the estrogen receptor is a marked difference in the effect of the drug in different tissues. A good example is the breast cancer drug tamoxifen which shows antagonist effects in breast tissue but agonist effects in uterine, bone and cardiovascular tissue. Other drugs have different tissue profiles. Our lab has identified one possible molecular mechanism behind these differences. The two subtypes of the estrogen receptor (ER-alpha and ER-beta) have different responses to estradiol, tamoxifen and raloxifene at an AP-1 response element. My project is to determine the key structural features on the ligands and receptors responsible for these differences using hybrids of the receptor as well as hybrid molecules. Crystal structures have been reported for ER-alpha bound to estradiol, raloxifene and tamoxifen. The Computer Graphics Laboratory facilities allows me to use these structures to assist in my ligand design as well as to assess possible interactions with new compounds that I have made.